Cathepsin S (CTSS), a proteolytic enzyme, plays an essential role in the major histocompatibility complex (MHC) class II antigen presentation pathway. Specifically, this enzyme degrades the invariant chain (a MHC class II chaperone) prior to its removal from the MHC class II peptide-binding cleft. This facilitates loading of antigenic amide compounds to MHC class II αβ-dimers and subsequent transportation of the complex to the cell surface to initiate MHC class II restricted CD4+ T-cell recognition. See Pierre and Mellman, Cell 1998, 93, 1135-1145. It has been found that CTSS is associated with autoimmune and inflammatory diseases, such as asthma, allergy, atherosclerosis, emphysema, and rheumatoid arthritis.
CTSS also participates in dissolution and remodelling of connective tissue and basement membranes in tumor growth, invasion, and metastasis. See Sloane et al., Biochemical and Molecular Aspects of selected Cancers, 1994, 411-466, Academic Press, New York Inhibition of this enzyme has been reported to be effective in treating cancers. See Reise et al., Immunity 1996, 4, 357-366 and Liu et al., Drug News Prespect 2004, 17, 357-363.